Community acquired pneumonia (CAP) was reported in 35.6% of patients enrolled in a phase III trial of drotrecogin alfa (activated) in severe sepsis (PROWESS). 28 days following infusion, the relative risk reduction (RRR) in CAP was 27.8% (p = 0.015). We report in-hospital and 90-day survival for patients with CAP including Streptococcus pneumoniae.
CAP was defined as: (1) lung identified as primary site of infection as determined by a blinded clinical evaluation committee (CEC) (2) admission to hospital from home, and (3) receipt of study drug within 4 days of hospital admission. The CEC also adjudicated causative microorganism(s) responsible for severe sepsis in each patient. Mortality relative risk estimates with 95% confidence intervals (CIs) were calculated for each subgroup.
In the overall PROWESS population, treatment with drotrecogin alfa (activated) yielded a 19.4% adjusted RRR in all-cause mortality at day 28, p=0.005. Of the 602 patients with any CAP, 46% received placebo and 54% received drotrecogin alfa (activated). Hospital mortality for CAP was 27.0% for drotrecogin alfa (activated) and 35.4% for placebo, an absolute risk reduction of 8.4% and a RRR of 23.8% (relative risk = 0.762, 95% CI = 0.598 – 0.971). At 90 days, mortality for CAP was 33.8% for drotrecogin alfa (activated) and 39.5% for placebo (RRR = 14.4%, relative risk = 0.856, 95% CI = 0.688 – 1.065). Of the 157 patients with CAP due to S. pneumoniae, 52% received placebo and 48% received drotrecogin alfa (activated). In the S. pneumoniae subgroup, hospital and 90-day mortality rates for drotrecogin alfa (activated) were 26.4% and 31.8% and for placebo 37.5% and 38.8%, respectively. RRR for patients with S. pneumoniae was 29.6% in hospital and 17.9% at 90 days.CONCLUSIONS: The survival benefit associated with drotrecogin alfa (activated) is maintained 28 to 90 days after treatment for any CAP including S. pneumoniae.CLINICAL IMPLICATION: A long-term survival benefit in CAP from drotrecogin alfa (activated) was similar to the overall PROWESS trial.
R.G. Wunderink, Eli Lilly and Company, Discussion of product research or unlabeled uses of Product.